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目的:优化制备K237多肽修饰的紫杉醇隐形纳米粒(K237-PTX-NP),并评价其对HCT-15和HUVEC两种细胞的细胞毒性。方法:乳化-溶剂挥发法优化制备K237-PTX-NP;HPLC法测定其包封率、载药量;激光粒度分析仪测定其粒径和Zeta电位;CBQCA试剂盒测定纳米粒表面多肽密度。以Taxol和PTX-NP为对照,采用CCK-8方法研究比较K237-PTX-NP对HCT-15和HUVEC细胞的细胞毒性差异。结果:优化制备的K237-PTX-NP粒径为约150 nm,Zeta电位为-20 mv,包封率为33.5%,载药量为2.8%,多肽连接效率为24.5%,平均每个纳米粒表面连接的K237数目约为474个。作用24 h时,K237-PTX-NP抑制HUVEC活性的IC50为0.01 nM,而抑制HCT-15活性的IC50大于1μM。结论:与HCT-15相比,HUVEC对K237-PTX-NP高度敏感,提示K237-PTX-NP具有潜在通过抑制肿瘤血管内皮细胞的生长治疗以HCT-15为代表的、P-gp等膜转运蛋白高表达的耐药肿瘤的能力。
OBJECTIVE: To optimize preparation of K237-PTX-NP paclitaxel modified with K237 polypeptide and evaluate its cytotoxicity on both HCT-15 and HUVEC cells. Methods: K237-PTX-NP was prepared by emulsion-solvent evaporation method. The entrapment efficiency and drug loading were determined by HPLC. The particle size and Zeta potential were measured by laser particle size analyzer. The peptide density was measured by CBQCA kit. Using Taxol and PTX-NP as control, the cytotoxicity of K237-PTX-NP on HCT-15 and HUVEC cells was compared by CCK-8 assay. Results: The optimal particle size of K237-PTX-NP was about 150 nm, the zeta potential was -20 mv, the entrapment efficiency was 33.5%, the drug loading was 2.8%, and the polypeptide connection efficiency was 24.5% The number of surface-connected K237s is about 474. The IC50 of K237-PTX-NP for inhibiting HUVEC activity was 0.01 nM and the IC50 for inhibiting HCT-15 activity was greater than 1 μM for 24 h. CONCLUSIONS: HUVECs are highly sensitive to K237-PTX-NP compared to HCT-15, suggesting that K237-PTX-NP has the potential to inhibit the growth of tumor vascular endothelial cells by treatment of HCT-15, P-gp and other membrane transporters The ability of proteins to overexpress resistant tumors.